Protein kinase Cdelta activates RelA/p65 and nuclear factor-kappaB signaling in response to tumor necrosis factor-alpha
- PMID: 19549902
- DOI: 10.1158/0008-5472.CAN-08-4786
Protein kinase Cdelta activates RelA/p65 and nuclear factor-kappaB signaling in response to tumor necrosis factor-alpha
Abstract
Nuclear factor-kappaB (NF-kappaB) is tightly modulated by IkappaB kinases and IkappaBalpha in the cytoplasm. On stimulation, NF-kappaB translocates into the nucleus to initiate transcription; however, regulation of its transcriptional activity remains obscure. Here, we show that protein kinase C (PKC) delta controls the main subunit of NF-kappaB, RelA/p65. On exposure to tumor necrosis factor-alpha (TNF-alpha), the expression of RelA/p65 target genes such as IkappaBalpha, RelB, and p100/p52 is up-regulated in a PKCdelta-dependent manner. The results also show that PKCdelta is targeted to the nucleus and forms a complex with RelA/p65 following TNF-alpha exposure. Importantly, kinase activity of PKCdelta is required for RelA/p65 transactivation. In concert with these results, PKCdelta activates RelA/p65 for its occupancy to target-gene promoters, including IkappaBalpha and p100/p52. Moreover, functional analyses show that inhibition of PKCdelta is associated with substantial attenuation of NF-kappaB activity in response to TNF-alpha. These findings provide evidence that PKCdelta orchestrates RelA/p65 transactivation, a requisite for NF-kappaB signaling pathway in the nucleus.
Similar articles
-
Honokiol inhibits TNF-alpha-stimulated NF-kappaB activation and NF-kappaB-regulated gene expression through suppression of IKK activation.Biochem Pharmacol. 2005 Nov 15;70(10):1443-57. doi: 10.1016/j.bcp.2005.08.011. Epub 2005 Sep 21. Biochem Pharmacol. 2005. PMID: 16181613
-
RelA repression of RelB activity induces selective gene activation downstream of TNF receptors.Proc Natl Acad Sci U S A. 2005 Oct 11;102(41):14635-40. doi: 10.1073/pnas.0507342102. Epub 2005 Sep 28. Proc Natl Acad Sci U S A. 2005. PMID: 16192349 Free PMC article.
-
Pim-1 controls NF-kappaB signalling by stabilizing RelA/p65.Cell Death Differ. 2010 Apr;17(4):689-98. doi: 10.1038/cdd.2009.174. Epub 2009 Nov 13. Cell Death Differ. 2010. PMID: 19911008
-
Phosphorylation of NF-kappaB and IkappaB proteins: implications in cancer and inflammation.Trends Biochem Sci. 2005 Jan;30(1):43-52. doi: 10.1016/j.tibs.2004.11.009. Trends Biochem Sci. 2005. PMID: 15653325 Review.
-
The alternative NF-kappaB pathway from biochemistry to biology: pitfalls and promises for future drug development.Biochem Pharmacol. 2006 Oct 30;72(9):1161-79. doi: 10.1016/j.bcp.2006.08.007. Epub 2006 Sep 12. Biochem Pharmacol. 2006. PMID: 16970925 Review.
Cited by
-
Protection against sepsis-induced lung injury by selective inhibition of protein kinase C-δ (δ-PKC).J Leukoc Biol. 2011 Jan;89(1):3-10. doi: 10.1189/jlb.0510281. Epub 2010 Aug 19. J Leukoc Biol. 2011. PMID: 20724665 Free PMC article.
-
Protein kinase C-δ (PKCδ) regulates proinflammatory chemokine expression through cytosolic interaction with the NF-κB subunit p65 in vascular smooth muscle cells.J Biol Chem. 2014 Mar 28;289(13):9013-26. doi: 10.1074/jbc.M113.515957. Epub 2014 Feb 11. J Biol Chem. 2014. PMID: 24519937 Free PMC article.
-
Trimeric G protein-CARMA1 axis links smoothened, the hedgehog receptor transducer, to NF-κB activation in diffuse large B-cell lymphoma.Blood. 2013 Jun 6;121(23):4718-28. doi: 10.1182/blood-2012-12-470153. Epub 2013 Apr 30. Blood. 2013. PMID: 23632891 Free PMC article.
-
The NF (Nuclear factor)-κB inhibitor parthenolide interacts with histone deacetylase inhibitors to induce MKK7/JNK1-dependent apoptosis in human acute myeloid leukaemia cells.Br J Haematol. 2010 Oct;151(1):70-83. doi: 10.1111/j.1365-2141.2010.08319.x. Epub 2010 Aug 2. Br J Haematol. 2010. PMID: 20701602 Free PMC article.
-
PKCδ Mediates NF-κB Inflammatory Response and Downregulates SIRT1 Expression in Liver Fibrosis.Int J Mol Sci. 2019 Sep 17;20(18):4607. doi: 10.3390/ijms20184607. Int J Mol Sci. 2019. PMID: 31533364 Free PMC article.
Publication types
MeSH terms
Substances
LinkOut - more resources
Full Text Sources
